Rhodium-Catalyzed Cyclopropanation of Fluorinated Olefins: A Straightforward Route to Highly Functionalized Fluorocyclopropanes

Abstract

An efficient access to highly functionalized monofluorocyclopropanes is described. The developed methodology allowed straightforward access to a large panel of polysubstituted fluorinated cyclopropanes in good to excellent yields and good diastereoselectivities. The Rh-catalyzed cyclopropanation proved to be efficient on several fluorinated olefins and several diazo compounds. This method represents the first general route to complex fluorinated cyclopropanes.

Asymmetric Synthesis of Fluoro, Fluoromethyl, Difluoromethyl, and Trifluoromethylcyclopropanes

“…Considering the limitation of the proof of concept brought by Haufe, we first studied the use of nonchiral rhodium catalysts to perform the cyclopropanation of highly functionalized di- or trisubstituted fluoroalkenes with diacceptor diazo compounds (Scheme ). This methodology would allow access to various classes of fluorinated cyclopropanes, which can undergo subsequent functional group manipulations to broaden the portfolio of existing fluorocyclopropanes. The optimization of the reaction conditions highlighted Rh 2 (OPiv) 4 and Rh 2 (esp) 2 as preferred catalysts for the cyclopropanation of a large panel of fluorinated olefins with highly functionalized diazo derivatives, such as α-cyanodiazoacetates, α-nitrodiazoacetates, α-nitrodiazoketones or diazomalonates.…”

Fluorine containing cyclopropanes: synthesis of aryl substituted all-cis 1,2,3-trifluorocyclopropanes, a facially polar motif

“…8 Jubault's lab have made recent contributions to the synthesis of more highly functionalised monofluorocyclopropanes. 9 Good methods have developed to prepare -difluorocyclopropanes through difluorocarbene addition to olefins, 10 and a very wide range of such compounds have been prepared, and this category of fluorinated cyclopropane dominates entries in the chemical and patent literature. Vicinal or '-di-fluorocyclopropanes are rarely quoted, where the fluorines are located on two adjacent carbons, rather than as a CF 2 group.…”

Synthesis and Applications of Fluorocyclopropanes

“…In 2015, our groups reported the rhodium-catalyzed formation of highly functionalized fluorocyclopropane (Scheme 2). 10 The developed methodology was applied to a broad range of fluoroalkenes, included O-protected fluoroallylic alcohols, fluoroallyl chloride, and fluoroallylphosphonates with various acceptor/acceptor diazo compounds (EWG = CO 2 R, CN, NO 2 , COR). The use of Rh 2 (OPiv) 4 (0.5 mol%) or Rh 2 (esp) 2 (1-2 mol%) as a catalyst allowed the formation of the corresponding fluorocyclopropanes in good to excellent yields (33-94%) and moderate to excellent diastereoselectivities (up to 99:1).…”